1. Technical Field
The invention relates to octahydro-pyrrolo[3,4-b]pyrrole compounds, compositions comprising such compounds, particular salts and polymorphs thereof, methods for making the compounds, salts, and polymorphs, and methods of treating conditions and disorders using such compounds and compositions.
2. Description of Related Technology
Histamine is a well-known modulator of neuronal activity. At least four types of histamine receptors have been reported in the literature, typically referred to as histamine-1, histamine-2, histamine-3, and histamine-4. The class of histamine receptor known as the histamine-3 receptor (also sometimes called the histamine H3 receptor or the H3 receptor) is believed to play a role in neurotransmission in the central nervous system.
The histamine-3 (H3) receptor was first pharmacologically characterized on histaminergic nerve terminals (Nature, 302:832-837 (1983)). The histamine H3 receptor is able to regulate the release of neurotransmitters in the central nervous system and peripheral nervous system, and also in peripheral organs such as the gastrointestinal tract. Histamine H3 ligands have been shown to be able to modulate the release of histamine, dopamine, serotonin, acetylcholine, and other neurotransmitters. The existence of H3 receptors and their established role in modulating neurotransmitter release activity in animal models of disease indicate the utility of histamine H3 ligands for the treatment of disease. This has motivated a search for, and the development of, selective H3 receptor agonists and antagonists ((Leurs, et al., “The histamine H3 receptor: From gene cloning to H3 receptor drugs” Nature Reviews Drug Discovery (2005) v. 4, p 107-120; Arrang, et al. Nature, 327:117-123 (1987); Leurs and Timmerman, ed. “The History of H3 Receptor, a Target for New Drugs,” Elsevier (1998)).
The activity of histamine H3 receptors can be modified or regulated by the administration of histamine H3 receptor ligands. The ligands can demonstrate antagonist, inverse agonist, or partial agonist activity, For example, histamine H3 receptors have been linked to conditions and disorders related to the central nervous system involving memory, cognitive and other neurological processes, obesity, and also peripheral and systemic activities, such those involved in asthma and allergic rhinitis. Although various classes of compounds demonstrating H3 receptor-modulating activity exist, it would be beneficial to provide additional compounds demonstrating activity at the H3 receptors that can be incorporated into pharmaceutical compositions useful for therapeutic methods.